Current Research
My laboratory is concerned with elucidating the processes that control developmental regulation of cardiac ion channel expression (i.e. electrical behavior) and cardiac autonomic responsiveness (i.e. sensitivity to neurotransmitters), and using that knowledge to design gene- and cell-based therapies for cardiac disease.

We study heart cells grown alone in culture, or co-cultured with neurons or mesenchymal stem cells. We employ a range of techniques, including standard electrophysiology, whole cell voltage clamp and fluorescence microscopy with ion sensitive dyes. By studying both native cardiac channels and recombinant channels over-expressed in myocytes we explore the molecular mechanisms that control channel function within the heart cell and the impact of development and disease on these mechanisms. We also take advantage of transgenic animals in which selected signaling elements have been disrupted or altered.

We have identified age-dependent differences in the function and expression of several cardiac ionic channels (including INa, ICa,L and If), and also differences in autonomic signal transduction cascades (including alpha- and beta-adrenergic and cholinergic) that modulate these and other ionic channels in the heart. We have further found that neurons exert a trophic influence to modify heart cell development that can account for some of the age-dependent effects on ion channel function and the cardiac cell's response to autonomic agonists. Both neurally released peptides (e.g. NPY) and more familiar neurotransmitters (e.g. norepinephrine) can serve as developmental factors.

Our increasing understanding of the factors that regulate channel function within the heart cell allows us to develop genetic therapies in which selected channels are over-expressed in the in situ heart, either within the myocytes or in stem cells that then couple to the myocytes, for the purpose of regulating cardiac rhythm. Recent efforts in this regard have resulted in proof-of-concept studies creating a biological pacemaker to augment or replace current electronic pacemakers and enhancing conduction to disrupt reentrant arrhythmias associated with myocardial infarction.